High-Throughput Drug Testing and Synergy Evaluation in Patient-Derived Tumor Organoids: A Practical Guide

High-throughput drug testing combined with synergy evaluation in patient-derived tumor organoids (PDOs) represents a robust methodological approach to identify effective therapeutic combinations. PDOs retain tumor heterogeneity and the three-dimensional microenvironment, offering a physiologically relevant platform for rational drug testing. In this chapter, we provide a methodological guide to synergy testing in PDOs, including experimental design, statistical frameworks, and troubleshooting strategies. Emphasis is placed on practical aspects of drug combination screening, interpretation of synergy scores, and considerations for reproducibility. This practical guide aims to support researchers in applying organoid-based synergy assays as a translational tool in oncology.